SP1 - MelAutim
Targeting the crosstalk between melanoma and immune cells by reprogramming the cancer secretome
In this project we will investigate how the cells of the malignant melanoma influence the cells of the immune system by releasing messenger substances. In their complexity, these messenger substances are called secretome. Thus, we will investigate how the cancer cells enable the progression of the tumor disease and resistance to the immune system, as well as a flare-up of pre-existing autoimmune diseases. We focus on the actions of an important cellular protein, the transcription factor E2F1. E2F1 plays a special role in cancer cells because it is involved in the formation of metastases. In this regard, we want to find out to what extent E2F1 can induce and control immunomodulatory properties of the melanoma secretome in tumor cells. E2F1 performs this prometastatic function in interaction with many other cofactors, of which more are constantly being discovered, and their function will be investigated. Within this growing repertoire of coregulators, the aim is to find those cofactors which, together with E2F1, increase the activity of target genes that perform immunomodulatory functions. Finally, we will identify so-called E2F1/cofactor/target gene axes that re-program the secretome to downregulate the immune response against the tumor cells in favour of tumor progression. Once within cancer cells such axes are identified, research can begin to develop mechanisms that interfere with these axes, for example ones that prevent the rapid spread of the very dangerous skin cancer. At the same time, we expect to gain insights into how the (re)occurrence of autoimmune diseases can be suppressed in the context of cancer.